Short-term treatment of Graves' disease with methimazole in high versus low doses

Abstract. Objectives . To compare the relapse rates in Graves' disease the first 2 years after methimazole 60 mg day^?1 combined with thyroxine versus a titration regimen with methimazole alone, and to look for possible prognostic factors. Design . A randomized, open, prospective study. Methimazole was given for 6 months in both groups, and thyroid status evaluated every 3rd month during the first year, and every 6th month during the second year. Setting . The study was performed at our outpatient clinic with patients referred from primary care. Subjects . Fifty-six patients were included. One became pregnant and one dropped out during the treatment period. Furthermore, nine patients in the high-dose and four in the low-dose group stopped the treatment because of side-effects. Thus, 19 patients in the high- and 22 in the low-dose group completed 6 months with methimazole. Results . In those tolerating the treatment, the relapse rates in the high- and low-dose groups were 26.3 vs. 59.1% (P < 0.05), 42.1 vs. 77.3% (P < 0.02); and 57.9 vs. 77.3% (NS) after 3, 12 and 24 months, respectively. The corresponding relapse rates calculated on an ‘intention to treat’ basis were: 51.7 vs. 66.7%; 62.1 vs. 81.5%; 72.4 vs. 81.5% (NS). The thyroid volume was significantly (P < 0.05) larger in those that relapsed (17.8 ± 2.9 vs. 11.6 ± 1.2 mL; mean ± SEM). Conclusions . In those tolerating the treatment, methimazole significantly reduced the relapse rate the 1st year when given in a high dose. However, the relapse rates in both groups, and the number of side-effects in the high-dose group, were unacceptably high.